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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q96P20: Variant p.Val200Met

NACHT, LRR and PYD domains-containing protein 3
Gene: NLRP3
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Variant information Variant position: help 200 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Valine (V) to Methionine (M) at position 200 (V200M, p.Val200Met). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In FCAS1 and MWS. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 200 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1036 The length of the canonical sequence.
Location on the sequence: help QQEREQELLAIGKTKTCESP V SPIKMELLFDPDDEHSEPVH The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         QQEREQELLAIGKT--KTCESPVSPIKMELLFDPDDEHSEPVH

Rhesus macaque                QQEREHELLAIGKT--KTWESPVSPIKMELLFDPDDEHSEP

Mouse                         KQEREHELLTIGRT--KMRDSPMSSLKLELLFEPEDGHSEP

Rat                           KQEREHELLTIGRT--KMWDRPMSSLKLELLFEPEDEHLEP

Bovine                        QQEREHELLAIGRTWAKIQDSPVSSVNLELLFDPEDQHSEP
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 1036 NACHT, LRR and PYD domains-containing protein 3
Domain 140 – 210 FISNA
Modified residue 198 – 198 Phosphoserine
Modified residue 198 – 198 Phosphoserine; by MAPK8
Modified residue 201 – 201 Phosphoserine
Mutagenesis 198 – 198 S -> A. Abolished phosphorylation by MAPK8/JNK1; decreased activation of the NLRP3 inflammasome.
Mutagenesis 198 – 198 S -> DE. Mimicks phosphorylation state; increased activation of the NLRP3 inflammasome.
Mutagenesis 213 – 213 D -> R. Does not affect ability to activate the NLRP3 inflammasome.



Literature citations
Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome.
Hoffman H.M.; Mueller J.L.; Broide D.H.; Wanderer A.A.; Kolodner R.D.;
Nat. Genet. 29:301-305(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2); VARIANTS FCAS1 MET-200; VAL-441 AND GLY-629; VARIANT MWS VAL-354; Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis.
Aganna E.; Martinon F.; Hawkins P.N.; Ross J.B.; Swan D.C.; Booth D.R.; Lachmann H.J.; Gaudet R.; Woo P.; Feighery C.; Cotter F.E.; Thome M.; Hitman G.A.; Tschopp J.; McDermott M.F.;
Arthritis Rheum. 46:2445-2452(2002)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3); VARIANT MWS MET-200; VARIANTS FCAS1/MWS TRP-262 AND PRO-307; New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes.
Dode C.; Le Du N.; Cuisset L.; Letourneur F.; Berthelot J.-M.; Vaudour G.; Meyrier A.; Watts R.A.; Scott D.G.I.; Nicholls A.; Granel B.; Frances C.; Garcier F.; Edery P.; Boulinguez S.; Domergues J.-P.; Delpech M.; Grateau G.;
Am. J. Hum. Genet. 70:1498-1506(2002)
Cited for: VARIANT FCAS1 MET-200; VARIANTS MWS ASN-305; MET-350; THR-441 AND ARG-571; VARIANT FCAS1/MWS TRP-262; Clinical and genetic heterogeneity among Spanish patients with recurrent autoinflammatory syndromes associated with the CIAS1/PYPAF1/NALP3 gene.
Arostegui J.I.; Aldea A.; Modesto C.; Rua M.J.; Argueelles F.; Gonzalez-Ensenat M.A.; Ramos E.; Rius J.; Plaza S.; Vives J.; Yaguee J.;
Arthritis Rheum. 50:4045-4050(2004)
Cited for: VARIANTS FCAS1 MET-200; PRO-307 AND LYS-490; VARIANT CINCA ASN-305; VARIANT MWS MET-350;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.